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Case Presentation



dr. Novi Yanti Sari

dr. Irmalita, Sp.JP(K)


JUNE 2015


Chronic thromboembolic pulmonary hypertension (CTEPH) is one of subgroups of

pulmonary hypertension. This is a serious medical condition that sometimes under diagnosed.
CTEPH is commonly underdiagnosed due to non specific symptoms and lack of diagnostic
tools. CTEPH is an important cause of severe pulmonary hypertension usually occurring as a
long-term complication of pulmonary embolism. Previously the condition was thought to be
rare, but recent studies have estimated that 3.8% of patients with a pulmonary embolus may
subsequently develop CTEPH. The severity of the disease depends on the degree of the
underlying associated pulmonary hypertension and right heart dysfunction. CTEPH is
responsible for significant levels of morbidity and mortality, especially when left untreated.
We present a 74 years old male with history of progressive dyspnea on exertion, which
prompted ER consult and hence admission. Further history taking, physical examination, and
echocardiography were suggestive of pulmonary hypertension. No deep vein thrombosis
(DVT) was found on vascular femoral sonography. It was found after the lung perfusion
scintigraphy performed that she actually had CTEPH. CTPA have not yet been performed in
this case, and will be done in outpatient settings.

Keyword: chronic thromboembolic pulmonary hypertension


Pulmonary hypertension has been defined as an increase in mean pulmonary arterial

pressure (PAP) more than 25 mmHg at rest as assessed by right heart catheterization (RHC).1
Chronic thromboembolic pulmonary hypertension (CTEPH) is one of subgroups of pulmonary
hypertension characterised by mechanical obstruction of the pulmonary arteries, which is
caused by the presence of organised fibrotic thrombi tightly attached to the medial layer of the
elastic pulmonary arteries, replacing the normal intima. This thromboembolic material may
completely occlude the lumen of the affected artery, with associated pitting or roughening of
the intimal surface, formation of bands and webs traversing the vascular lumen and partial
This is a serious medical condition that sometimes under diagnosed. CTEPH is
commonly underdiagnosed due to non specific symptoms and lack of diagnostic tools. CTEPH
is an important cause of severe pulmonary hypertension usually occurring as a long-term
complication of pulmonary embolism. Previously the condition was thought to be rare, but
recent studies have estimated that 3.8% of patients with a pulmonary embolus may
subsequently develop CTEPH.3 The severity of the disease depends on the degree of the
underlying associated pulmonary hypertension and right heart dysfunction.2 CTEPH is
responsible for significant levels of morbidity and mortality, especially when left untreated.4
The exact prevalence of CTEPH is still unknown. In the United States, registry data
suggest that the incidence of CTEPH is between 3 and 30 per 1 million in the general
population. It is estimated that an acute PE occurs in 0.5 to 0.6 million individuals each year,
and CTEPH occurs in 3.8% of patients with a history of acute pulmonary embolism (PE).4 This
figure may underestimate the true frequency of CTEPH, as the disease is often misdiagnosed
because of nonspecific symptoms and a variable disease course. This is hindered by the
observation that up to 40-60% of the patients have no known history or clinically apparent of
acute pulmonary embolism episodes.4

The aim of this case report is to discuss the etiology, risk factors, diagnosis and
management of chronic thromboembolic pulmonary hypertension.


A 74 years old male was brought to the Emergency department in NCCHK with chief
complaint of difficulty of breathing. History of present illness started around 1 month prior to
admission, where he started to have episodes of dyspnea on exertion, which progressed slowly
but become worsened every time. This was followed by two to three pillows orthopnea,
paroxysmal nocturnal dyspnea, and mild ankle edema. There was no history of syncope, chest
pain, palpitation, or hemoptysis. He denied any history of asthma, previous lung infection,
prolonged immobilization or previous surgery. His comorbidities include diabetes and
hypertension. He was maintained on Metformin 500mg b.i.d, Lisinopril 10mg o.d, Furosemide
40mg b.i.d, Bisoprolol 5mg o.d. He denied history of congenital heart disease in the family.
Upon examination, he was fully alert with blood pressure of 166/80 mmHg, heart rate
of 125 beats per minute, respiratory rate of 24 times per minute and a 100% peripheral oxygen
saturation. His conjunctiva were not anemic and the sclera were not icteric. Jugular venous
pressure was 5+3 cmH2O. Heart auscultation revealed normal first heart sound with
accentuated pulmonary component of second heart sound. No murmur nor gallop were
appreciated. The breath sound was vesicular in both lungs, with minimal basal rales, no
wheezing was heard. On abdomen examination ascites (+), with palpable liver approximately
2 cm below costal border, and peristaltic sound was normal. Extremities were warm and there
were minimal pretibial edema in both feet. No peripheral cyanosis were noted.
Electrocardiography (ECG) showed atrial tachycardia with QRS rate 125 beats per
minute, normal QRS axis, QRS duration of 0.08 seconds, left ventricular hypertrophy and strain
(Figure 1). Chest X-ray showed 48% of cardiothoracic ratio with normal aortic segment. The
pulmonic segment was normal with the cardiac apex pointing downward. Cardiac waist was
normal, without sign of infiltration nor congestion (Figure 2).

Figure 1. Electrocardiography

Figure 2. Chest X-Ray of the patient

Laboratory examination of routine hematology, renal function, electrolyte, liver

function are within normal limit. However D dimer was elevated at 1135, and fibrinogen at 65.
Echocardiography showed right atrial dilatation, concentric left ventricular hypertrophy
(LVH), D shaped LV, normal left ventricular systolic function with 61% ejection fraction, and
reduced right ventricular function with tricuspid annular plane systolic excursion (TAPSE) of
1.2 cm. There were mild to moderate tricuspid regurgitation with tricuspid valve gradient

(TVG) of 41 mmHg, mild mitral regurgitation and pulmonary regurgitation with mPAP of
15mmHg. Left atrium was within normal limit with no thrombus was visible. (Figure 3).

Figure 3. Echocardiography

On admission at the emergency department, the patient was given furosemide 80mg IV
to relieve congestion symptoms and digoxin 0.5mg IV for rate control. He was then transferred
to adult ward to continue his treatment. He was maintained on furosemide drip started at
5mg/hour and was titrated accordingly. Digoxin was given regularly at dose of 0.25mg o.d.
Heparin drip was also started and was given overlapping with warfarin 2mg o.d. On his 3rd day
of hospitalization, lung perfusion scan and vascular femoral sonography were performed.
Vascular femoral sonography examination revealed normal flow on arteries and veins.
There were no sign of chronic venous insufficiency nor deep vein thrombosis at both lower
Lung perfusion scan was then performed. On the right lung, segmental perfusion was
detected in apical and upper lobe. On the left lung, segmental perfusion defects were also
detected in the posterior segment of upper lobe, lingula, anterobasal, and mediobasal of lower
lobe (Figure 4). It was concluded from the lung perfusion scan that there were chronic
pulmonary embolism at the left lung. Hence Sildenafil 12.5mg t.i.d was added to his therapeutic
regimen. Chest CT scan and pulmonary angiography was not yet performed in this patient and
will be done in outpatient clinic after discharge.

Figure 4. Lung perfusion scan

CTEPH is characterized by intraluminal thrombus organization and fibrous stenosis or
complete obliteration of pulmonary arteries.5 The consequence is an increased pulmonary
vascular resistance resulting in pulmonary hypertension and progressive right heart failure.6
CTEPH occurs in about 0.5% to 4% of patients with a history of PE. International
registry of CTEPH reported a history of acute PE in 74.8% of CTEPH patients and 56.1% with
previous deep vein thrombosis.5 This is in contrasts with previous retrospective reports
indicating no history of venous thromboembolism in 40% to 60% of the patients.6 It is possible
that PE is simply undiagnosed in some patients. In the majority of patients, months or even
years (the so-called honeymoon period) may pass after PE before clinically significant
pulmonary hypertension manifests. This presumed gradual progression of pulmonary
hypertension occurs in the absence of documented recurrent pulmonary embolic events and is
thought to reflect progressive remodeling of the unobstructed pulmonary vasculature,
stimulated by increased blood flow through these vessels. When there is no history of PE, the
etiology is uncertain.7
In our patient, no documented event of acute PE episode. But the symptoms started 1
month prior to hospital admission. He had no history of previous major surgery or prolonged
immobilization. However he had history of diabetes, and he was an ex active smoker. Diabetes
mellitus is a reported risk factor for VTE and pulmonary embolism (PE), and a meta-analysis
estimated a 1.4-fold increased risk of VTE for persons with diabetes.8-10 While former smoking
is related to cardiovascular diseases, diabetes, and certain types of cancer, which may be
associated with risk of VTE. Chronic inhalation of tobacco smoke, causing progressive lung

destruction, chronic obstructive pulmonary disease, and emphysema, may also result in a
hypercoagulable state and thus contribute to an increased risk of VTE.11 It is very likely that
this patient actually had silent pulmonary embolism at one time and had honeymoon period
before the first symptom developed.
Certain medical conditions are associated with an increased risk of CTEPH, including
previous splenectomy, the presence of a ventriculo-atrial shunt, infected pacemaker, previous
and recurrent VTE, chronic venous ulcers, thyroid hormone replacement therapy and
malignancy.10 In this patient, vascular femoral sonography found no deep vein thrombosis
(DVT) or other medical conditions associated with CTEPH. Thus, the diagnosis of CTEPH in
this patient was nearly missed.

Figure 6. Pathophysiological Features of the Pulmonary Vasculature in Chronic

Thromboembolic Pulmonary Hypertension12

Signs and symptoms

There are no specific signs or symptoms for CTEPH. The symptoms of CTEPH are
indistinguishable from other subgroups of PH, making the diagnosis more challenging.3
Patients generally present with progressive dyspnea on exertion, edema and/or signs of right
heart dysfunction including fatigue, chest pain and syncope. Cardiac auscultation may reveal
an accentuated pulmonic component to the second heart sound and delayed closure of the
pulmonic valve (split P2). Other signs may include a palpable left parasternal heave, a right
ventricular S3 or S4 gallop, prominence of the jugular A wave or V wave, hepatojugular reflux,
and lower extremity edema.2
In our patient, the symptoms started to occur 1 month prior to admission. At physical
examination, there was an accentuated pulmonic component of second heart sound. There were
an elevated JVP and hepatomegaly in the patient during his first examination at the ER.

Common electrocardiogram findings on PH include right atrial enlargement, right axis
deviation, and right ventricular enlargement, often with a strain pattern.11 T wave inversion,
representing the repolarization abnormalities associated with right ventricular hypertrophy, is
usually seen in the anterior precordial leads and may be mistaken for anteroseptal ischemia. 10
When ECG findings are present, they may be helpful prognostically because the presence of
right atrial enlargement has been associated with a 2.8-fold greater risk of death over a 6-year
period of observation, and RVH carried a 4.3-fold greater risk of death. And in one study,
increased P wave amplitude was found to correlate with worse survival.9
In our case, our patient had paroxysmal atrial tachycardia on the day of admission, and
after several days of rate treatment, it was converted back to sinus rhythm, but no right axis
deviation, right atrial enlargement, nor right ventricular hypertrophy were present. In this case,
we might conclude that our patient might be in the early stage of CTEPH, suggestive that if
early intervention were done, we might have better prognosis.

Chest X-ray examination

The chest X-ray can help determine the presence and cause of pulmonary hypertension,
but the findings are often nonspecific. Findings on the chest radiograph in the early stages of
CTEPH may be normal, but as disease progresses, signs that suggest the presence of PH include
an enlarged main and hilar pulmonary artery shadows with pruning or attenuation of
peripheral pulmonary vascular markings and right ventricle (RV) enlargement would be

occured. Central pulmonary artery enlargement often occurs with more advanced disease. The
lung fields may be clear, have areas of hypoperfusion (Westermark sign), or have evidence of
previous infarction (Hampton hump). The chest radiograph also allows to show findings
consistent with underlying disease processes, such as hyperinflation (COPD), kyphosis
(restrictive lung disease), or pulmonary venous congestion (pulmonary venous hypertension,
pulmonary veno-occlusive disease, or pulmonary capillary hemangiomatosis).11 Our patients
chest X-ray were not supportive, which showed no cardiomegaly with downward apex, and
normal pulmonal segment. Westermark sign and Hampton hump werent present. No sign of
lung disease or pulmonary venous congestion from the X-ray make the diagnosis of PH group
3 (due to lung disease) and PH group 2 (due to left heart disease) can be excluded.

Echocardiography has the advantage of detecting underlying causes or comorbidities,
such as leftsided cardiac disease, valvular abnormality, chamber mass, or intracardiac shunt.17
Findings on echocardiogram that are suggestive of elevated pulmonary pressure include
enlarged right atrium and ventricle, RV hypertrophy, globally reduced RV systolic function,
pulmonary artery dilatation, interatrial septal bowing to the left, and LV to appear D-shaped.
Value of pulmonary systolic pressure and tricuspid regugirtation velocity could be used to
determine the possibility of PH diagnosis.11

Diagnostic modalities of CTEPH

Diagnostic guideline of PH consist of recommendations based on evidence and
concepts that have evolved from formal research and observations that apply to general
populations. There have been numerous and evolving versions of diagnostic algorithms for the
evaluation of PH but all algorithms have consistently recommended the use of a radionuclide
ventilation/perfusion (V/Q) scan to screen for CTEPH. V/Q scans are particularly useful in
determining CTEPH and differentiating CTEPH from other causes of PH. V/Q scanning
demonstrated a sensitivity of 90%-100% and specificity of 94%-100% for differentiation
between idiopathic pulmonary arterial hypertension (IPAH) and CTEPH. Normal V/Q scan
rules out CTEPH and perfusion scans (rather than ventilation) are abnormal in virtually all
CTEPH patients. Recent data showed that 98.7% of patients had abnormal perfusion scans and
19.0% had abnormal ventilation scans. Underutilization of V/Q scans in screening PH invites
potential misdiagnosis of PAH. In the recent report from the Pulmonary Arterial Hypertension

Quality Enhancement Research Initiative registry in USA, 43% of PAH patients never had a
V/Q scan leading up to their diagnosis.12
CT pulmonary angiography (CTPA) has the advantage of being a non-invasive, cross
sectional technique with a spatial resolution close to conventional pulmonary angiography.
CTPA may reveal organized thrombi lining the proximal pulmonary vessels, abrupt tapering
or amputation of vessels or subtle intraluminal fibrous webs may be seen in CTEPH operable
patients. Other findings include dilatation of proximal pulmonary arteries and right heart
chambers, scarring and a mosaic perfusion pattern. Contrast-enhanced CTPA may be used as
a complementary tool in CTEPH but does not replace the ventilation/perfusion scan.
Eventhough multidetector CTPA had specificity of 99%, it only had sensitivity of 51% in
detecting CTEPH. Screening PH with only CT angiogram potentially misses CTEPH.12

Surgical pulmonary endarterectomy (PEA) has become the gold standard for curative
treatment of proximal CTEPH, resulting in a significant reduction of PA pressure and
improvement in right ventricular function, quality of life and survival.6 For our patients, the
PEA has not become a considerable option management since CTPA has not yet been
For medical management of CTEPH, the patient should receive life-long
anticoagulation (usually with oral vitamin K antagonists adjusted to a target INR between 2.0
and 3.0) to prevent in situ pulmonary artery thrombosis and recurrent venous
thromboembolism.1,2 Specific PAH drug therapy may still play a role in CTEPH patients,
especially when the surgical therapy is not an option (Class IIb, LOE C). The reason is from
the histopathological examination of distal arteries in CTEPH patients reveals vascular changes
similar to those in patients with idiopathic PAH and as in PAH. There are severals studies and
small trials suggesting benefits of endothelin receptor antagonists, Phosphodiesterase type 5
(PDE-5) inhibitors and prostanoid to CTEPH patient, but the data is still limited and requires
further studies. At present, no specific medical therapy has been widely approved for CTEPH.2
Our patients got heparin drip overlapping with warfarin for the oral anticoagulant,
diuretics and renin angiotensin aldosterone system (RAAS) blockers for the heart failure and
PDE-5 inhibitors as a pulmonary vasodilator during hospitalization. He was discharged
improved, and was planned to do evaluation after 3 months of therapy.


CTEPH is a distinct form of PH both in terms of its etiology and the way in which it responds
to treatment; it is the only subset of PH which is amenable to curative surgical intervention.
While existing epidemiological data have firmly established the thromboembolic nature of this
condition, there is still a large margin of error between different studies, the result of which is
that the exact prevalence and incidence of CTEPH remain unknown. CTEPH also sometimes
hard to diagnose due to its nonspecific symptoms, and without a proper and thorough
evaluation, this disease might be misdiagnosed.


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